From the desk of Zedie.
From the desk of Zedie.
High levels of the stress biomarker salivary alpha-amylase were associated with a greater likelihood of delayed pregnancy in women trying to conceive, according to researchers.
Women with the highest levels of alpha amylase at study entry, and following their first observed study menses, were twice as likely to fail to conceive over 12 months as women with the lowest levels of the stress biomarker (relative risk=2.07, 95% CI 1.04-4.11), reported Courtney Lynch, PhD, MPH, of The Ohio State University in Columbus, and colleagues, in Human Reproduction online.
This is the first U.S. study to show an association between stress — as measured by activation of the sympathetic adrenomedullary (SAM) pathway — and early infertility, the authors stated.
“We know that about one-third of infertility has an unknown cause,” Lynch told MedPage Today. “This tells us that by taking steps to reduce stress before attempting to become pregnant, many of these women may be able to optimize their fertility and avoid medical treatment. Stress may just be one small piece of the bigger picture in infertility, but I think it is a particularly interesting piece because it is something that a woman has the potential to change on her own.”
Until recently, most of the research examining stress and infertility has been from cross-sectional studies of couples seeking treatment for infertility, which were complicated by the fact that “the directionality of the association could not be determined,” her group wrote.
In a 2011 study done in a cohort in the U.K., Lynch and colleagues reported a prospective association between increased alpha-amylase and a 12% reduction in the day-specific probability of pregnancy, but this did not translate into a longer time-to-pregnancy (TTP), probably because the sample size was small at 274 women, Lynch said.
The current research was done using data collected from 2005 to 2009 as part of the Longitudinal Investigation of Fertility and the Environment (LIFE) Study, which enrolled 501 couples in Michigan and Texas at the time that they were discontinuing contraception for the purposes of becoming pregnant.
The couples were followed for up to 12 months as they tried to conceive and through pregnancy if it occurred. A total of 401 (80%) of the couples completed the study protocol and 373 (93%) had complete data available for the analysis.
After enrollment, the women collected saliva samples first thing in the morning, and then following their first observed study menses for the measurement of cortisol and alpha-amylase. The women were told to collect the samples before eating, drinking, smoking, or brushing their teeth.
The authors explained that “for the SAM system, norepinephrine is secreted into the bloodstream, which eventually results in an increase in salivary alpha-amylase production by the parotid gland.”
TTP was measured in cycles using journals and fertility monitors. Women’s daily journals also recorded bleeding, intercourse, periodic use of contraception, fertility monitor results, pregnancy test results, and other lifestyle data such as smoking and coffee consumption. Women were also asked to rate their daily stress level from 1 to 4, with 1 representing “almost no stress” and 4 representing “a lot of stress.”
The women had no known fertility problems when enrolled in the study and they had just started trying to conceive, suggesting that everyday stress, and not the specific stress associated with trying to become pregnant, affected their fertility, Lynch and colleagues wrote.
Among the 401 women who completed the protocol, 347 (87%) became pregnant and 54 (13%) did not over the course of a year.
No association was found between salivary cortisol levels and conception at 12 months, but after adjustment for age and several other factors known to influence fertility, women with the highest alpha-amylase had a 29% reduction in fecundity (longer time to pregnancy), compared with women in the lowest, expressed as a fecundability odds ratio (FOR 0.71, 95% CI 0.51-1.00. P<0.05).
In addition to the twofold increase in infertility risk and 29% reduction in fecundity among the women with highest and lowest tertiles of alpha-amylase levels, the analysis revealed that women in the middle tertile of salivary alpha-amylase had a 7% decreased odds of pregnancy after adjustment (FOR 0.93, 95% CI 0.68-1.29).
Women had similar times to pregnancy until around cycle five, at which time those in the highest tertile of alpha-amylase began to have lower pregnancy probabilities.
One study limitation cited was the inability to collect repeated saliva samples and perceived stress questionnaire data throughout the follow-up period. This made it impossible to determine if stress levels increased as the time to pregnancy increased.
Reproductive endocrinologist Tomer Singer, MD, of Lenox Hill Hospital in New York City, said other limitations included the relatively small sample size and homogeneity of the study cohort (83% were both non-Hispanic whites and college graduates), and the fact that 51% of the women had given birth prior to entering the study.
Singer also noted that the failure to show an association between cortisol levels and times to pregnancy, and the fact that several previous studies have failed to show a correlation between alpha-amylase levels and stress, makes the clinical implications of the research difficult to interpret.
The measurement of salivary alpha-amylase is considered a research assay only, and the test is not likely to be used in the clinical setting, he said.
“Despite the limitations, this is one of the first studies to measure what we have known in infertility for a very long time,” Singer told MedPage Today. “We see it in the practice setting all the time. Stress affects fertility. We just haven’t been able to tell our patients how.”
The U.S. is a melting pot — of ozone, particle and short-term pollution.
Every day, humans create a dangerous mix of harmful contaminants that are slowly but surely destroying our environment.
The American Lung Association produces a State of the Air report each year, which details the U.S. cities with the worst air pollution. Major states like California and Texas largely dominate the list, thanks to their size, with repeat offender cities such as Los Angeles, Houston and Dallas. In fact, the top three cities of 2013 stayed in the exact same spots.
Here are the top 10 U.S. cities with the worst air pollution in 2014.
Clayton Lockett’s death was not the first time something went wrong during an execution. A look at past bungled executions
The death of Clayton Lockett after a botched execution in Oklahoma on Tuesday night was not the first time something went wrong during a lethal injection. A look at recent and not-so-recent executions where things didn’t go as planned:
Executed: 16 January 2014
Drug protocol: A previously untested combination of two drugs – the sedative midazolam and painkiller hydromorphone – at concentrations that experts warned beforehand were so low the prisoner could endure cruel and unusual punishment.
What happened: A priest who was an eyewitness to the execution described the procedure as “ghastly” and “inhumane”. McGuire took 26 minutes to die, during which time he gasped audibly for air as he struggled to breath. A leading expert on anaesthesiology had warned Ohio that its protocol was inadequate and would inflict exactly the suffering that then appeared to play out. After an internal review, Ohio said this week it had done nothing wrong, but would nevertheless be increasing its dosages in future executions.
Executed: 9 January 2014
Drug protocol: Three-drug lethal injection starting with pentobarbital. As supplies of pentobarbital were running out following the European boycott of use of medicines in executions, Oklahoma turned to a compounding pharmacy to make up the pentobarbital. Compounding pharmacies are poorly regulated, and Oklahoma has refused to give any details of the source of the supply under new secrecy rules.
What happened: Within 20 seconds of the execution, Wilson said from the gurney: “I feel my whole body burning”.
Executed: 15 October 2013
Drug protocol: Happ was the first prisoner to be put to death using midazolam hydrochloride, a fast-acting sedative that had never been used before in executions, and the same drug deployed as the first of three lethal injections in Oklahoma last night.
What happened: Happ’s eyes opened and he blinked repeated for a prolonged period, and he yawned and his jaw opened. After an official pronounced him unconscious his head began moving again.
Executed: 27 September 2010
Drug protocol: Three-drug lethal injection starting with sodium thiopental which was the commonly-used old formula before sodium thiopental ran out in the wake of the European drug boycott of death penalty prisons.
What happened: It took about 30 minutes for officials to find a vein in which to inject the three drugs. Once that had been accomplished it took a further 14 minutes to kill him. Six days earlier, Rhode had tried to commit suicide by slashing his veins with a razor blade.
Execution: 15 September 2009
Drug protocol: Triple injection starting with sodium thiopental
What happened: Officials tried for more than two hours to find a useable vein, stabbing Broom with needles at least 18 times and making him scream and cry. At one point, the prisoner, lying on the gurney, tried to help the officials locate a vein. Eventually, the execution was stopped. Broom remains alive, awaiting a new execution date on death row.
Execution: 24 May 2007
Drug protocol: Triple injection
What happened: Newton, whose weight of about 265lbs allegedly contributed to difficulties, was allowed a bathroom break because it took the execution team over 30 minutes and 10 attempts with the needle to find a vein. At one point a prison official hung a sign before the viewing room glass that read “We have told the team to take their time. His size is creating a problem.” It took about 16 minutes, reportedly twice the average, before Newton was declared dead, during which time witnesses reported convulsions.
Execution: 2 May 2006
Drug protocol: Triple injection
What happened: The execution team “struggled for 25 minutes to find usable veins” (Clark had a history of drug use). The execution, which should have taken about 10 minutes, lasted almost an hour and a half. Witnesses said that “Clark raised his head, shook it back and forth, and repeatedly declared, ‘It don’t work,’” and that his moans were audible through the glass of the viewing room.
Ángel Nieves Díaz, 55
Execution: 13 December 2006
Drug protocol: Lethal injection
What happened: Executioners “pushed [the needles] all the way through the blood vessels into surrounding soft tissue”, rather than into his veins, leaving him with chemical burns on both arms. According to the Associated Press, “witnesses reported Diaz was moving as long as 24 minutes after the first injection, including grimacing, blinking, licking his lips, blowing and attempting to mouth words.” The execution took about 34 minutes. The duration of three-drug lethal injections vary depending on state protocol and the drugs involved, but the AP reports that this method would typically take 15 minutes, with the inmate unconscious after 3-5 minutes.
Brian Steckel, 36
Execution: 4 November 2005
Drug protocol: Triple injection
What happened: The machine meant to deliver the lethal drugs did not function correctly, forcing the execution team to switch to a backup device. They did not re-administer the sedative, however, leaving Steckel lucid throughout the 12 minutes it took for the drugs to take effect. He spoke throughout, and at one point looked to the warden and said, “I didn’t think it would take this long.”
Pedro Medina, 39
Execution: 25 March 1997
Method: Electric chair
What happened: Medina’s head caught fire from inside its mask after officials delivered electricity to the chair. A witness testified that Medina kept breathing for several seconds, saw smoke and smelled burning.
Jesse Tafero, 43
Execution: 4 May 1990
Method: Electric chair
What happened: On the electric chair Tafero’s head “burst into flame”, which officials blamed on the synthetic, “water-filled sponge attached to his head [to] conduct electricity from the electrode.” Prison officials then decided that “only sea sponges could enter the death chamber.”
Jimmy Lee Gray, 34
Execution: 2 September 1983
Method: Gas chamber
What happened: During the 47 minutes of the execution, Gray “foamed at the mouth and [beat] his head violently against a metal pole just behind the chair.” Executioners drew the blind on the viewing chamber after a few minutes.
Thomas Ketchum, 37
Execution: 26 April 1901
State: New Mexico
What happened: Because executioners had too much rope and built the gallows too tall, Ketchum fell with such force that “His head was severed from the body by the rope as if by a guilllotine,” as the San Francisco Chronicle told it at the time. “The headless trunk pitched forward toward the spectators and blood spurted upon those nearest the scaffold.”
William Kemmler, 30
Execution: 6 August 1890
State: New York
Method: Electric chair
What happened: Executioners declared Kemmler dead after 10 seconds, but a bleeding cut on his hand made them realize he was still alive. They turned the chair on twice more, during which time Kemmler convulsed and moaned, and after which he died.
Execution: 16 May 1879
State: Territory of Utah
Method: Firing squad
What happened: Seated before the squad, the volley of bullets only knocking him out of the chair while he screamed “Oh my God! My God! They have missed!” He bled to death 27 minutes later.
Execution: 17 May 1879
State: North Carolina
What happened: Executioners used rope that was too long, and had to raise the men off the ground, slowly strangling them.
Adults with a bachelor’s degree or higher are 81.9 percent more likely than those with less than a high school diploma to self-identify as “current regular drinkers”, according to the 2012 National Health Interview Survey (NHIS), which found that regular alcohol consumption increases with higher levels of education.
The NHIS – a “household, multistage probability sample survey conducted annually by interviewers of the U.S. Census Bureau for the Centers for Disease Control and Prevention’s National Center for Health Statistics”- collected data on 34,525 adults for the 2012 survey.
A “current regular drinker” was defined for the purposes of the study as someone who “had at least 12 drinks in his or her lifetime or in any 1 year AND had a drink 1-365 times in the past year.”
Just 35.3 percent of those with less than a high school diploma identified themselves as “current regular drinkers.” The percentage increased to 47.3 percent for those with a high school diploma or GED, and to 52.3 percent for those with some college.
However, the highest level of alcohol consumption was reported by people with college degrees: 64.2 percent of those with a bachelor’s degree or higher identified as “current regular drinkers”.
The study also revealed that young adults between the ages of 18 and 44 were the most likely to be regular drinkers, with 56.6 percent identifying as such.
In contrast, only 29,6 percent of those aged 75 and over drink alcohol regularly. And nearly a third (30.9 percent) of this demographic group are “lifetime abstainers,” according to the NHIS.
Another study conducted in 2010 by Maria del Carmen Huerta and Francesca Borgonovi of the London School of Economics entitled “Education, Alcohol Use and Abuse Among Young Adults in Britain” produced similar results.
The British study found that “higher educational attainment is associated with increased odds of daily alcohol consumption and problem drinking,” adding that “the relationship is stronger for females than males.”
“Both males and females who achieved high-level performance in test scores administered at ages five and 10 are significantly more likely to abuse alcohol than individuals who performed poorly on those tests,” the study found. (See Education, Alcohol Use and ABuse Among Young Adults in Britain.pdf)
“We find that a substantial part of the ‘educational effect’, especially among women, occurs because of the way in which educational attainment shapes social position and opportunities in life and by so doing promotes circumstances that favour alcohol consumption,” the British report concluded.
An infected scratch could become an everyday killer as antibiotics become increasingly useless, the world’s top doctors have warned.
The World Health Organisation said superbugs are now more deadly than the 80s Aids epidemic in a major report which declared, “the era of safe medicine is coming to an end”.
WHO Europe antimicrobial resistance adviser Dr Lo Fo Wong warned: “Everyone is potentially in danger.”
The WHO warned cash must urgently be pumped into developing new drugs after examining data from 114 countries.
The report warned of growing antibiotic resistance in seven bacteria linked to diseases such as sepsis, diarrhoea, pneumonia, urinary tract infections and gonorrhoea.
Dr Keiji Fukuda, assistant director general for health security, said: “Without urgent action, the world is headed for a post-antibiotic era in which common infections which have been treatable for decades can once again kill.”
England’s chief medical officer Dame Sally Davies has called for restrictions on prescribing antibiotics for mild infections and incentives for drugs firms to produce new medicines.
She said resistance was being fuelled because drugs were being unnecessarily used for mild infections.
Patients can help by only using prescribed antibiotics, making sure they complete the treatment and never sharing left-over prescriptions, the WHO said.
Microbiologist Prof Laura Piddock, of the University of Birmingham, said: “The world needs to respond as it did to the Aids crisis.
“We need a better understanding of resistance and development of new antibiotics.”
Bad weather and a delayed flight might be a recipe for misery – but in one instance 50 years ago it led to a discovery that has saved countless thousands of lives.
The discovery of the Epstein Barr virus – named after British doctor Anthony Epstein – resulted from his specialist knowledge of viruses which caused tumours in chickens plus his skills gained using one of the first commercially-available electron microscopes.
I had the feeling that this was something special”
Sir Anthony Epstein
His hunch was assisted by a longer than expected journey of some tumour cells from Uganda, which were nearly thrown in the bin.
But it would never have happened if Epstein’s curiosity hadn’t been fired up by a lecture by the Irish doctor turned “bush surgeon”, Denis Burkitt.
In the lecture, billed as a staff meeting on “The Commonest Children’s Cancer in Tropical Africa”, Burkitt described how he had noticed a number of cases of debilitating tumours which grew around the jawbone of children in specific regions – particularly those with high temperatures and high rainfall.
We now know this as Burkitt lymphoma.
Sir Anthony Epstein, now 93, speaking to the BBC’s Health Check programme, recalls: “I thought there must be some biological agent involved. I was working on chicken viruses which cause cancer. I had virus-inducing tumours at the front of my head. I thought… [it] was being carried by some insect vector, or some tic. That’s why it was temperature-related.”
The Epstein Barr virus belongs to the family of herpes viruses – and is linked to a number of different conditions, depending on where you live.
Most people are infected with the Epstein Barr virus. It’s best known in high-income countries for causing glandular fever which causes a sore throat, extreme fatigue and swollen glands in the neck.
According to Dorothy Crawford, emeritus professor of microbiology at Edinburgh University, up to 95% of all adults are infected with the virus.
“The virus is spread in childhood at different rates – in the saliva, so through close contact. In African countries most children have it by the age of two because they share cups in their household.
“The rate is lower in middle-class areas of England, so if you haven’t already been exposed by your early teens it can cause glandular fever.”
This has given it the nickname the kissing disease because, she explained: “People kissing in the back row of the cinema exchange more saliva than young children sharing toys.”
Epstein asked for samples of the tumours from Burkitt and they were sent back on overnight flights from Uganda.
For almost three years Epstein’s efforts to retrieve virus from the tumour cells failed, despite trying several culture methods used successfully for other viruses like influenza and measles.
In the end bad weather came to the rescue.
Fog delayed one flight which was diverted to Manchester, 200 miles from London. So the sample taken from the upper jaw of a nine-year-old girl with Burkitt lymphoma didn’t get to Epstein until late one Friday afternoon on 5 December 1963.
At that point it looked past its sell-by date.
“The fluid was cloudy. This suggested it had been contaminated on the way,” Epstein said.
“Was it full of multiplying bacteria? Before we threw it away I looked at it under a wet preparation microscope and saw huge numbers of free-floating, healthy looking tumour cells which had been shed from the edge of the tumour.”
Traditionally, growing cells successfully in culture had involved sticking them to a glass surface for support, but the lymphoma cells seemed to favour growing in a suspension.
Once all other conventional tests for identifying the virus from the cultured cells had failed, Epstein tried electron microscopy. The very first grid square he viewed included a cell filled with herpes virus.
Exhilarated by what he’d seen, Epstein went for a walk in the winter snow and came back feeling calmer.
“I was extremely frightened in case the electron beam [of the microscope] burned up the sample. I recognised at once the herpes virus – there were five then, now nine. Any of the then-known ones would have wiped the culture out when they were replicating but this wasn’t happening. I had the feeling that this was something special.”
Our understanding of this pervasive virus, named after Epstein and one of his PhD students Yvonne Barr who helped to prepare the samples, has increased over the years since Epstein confirmed his findings with American virologist colleagues.
Burkitt’s data helped to identify that the tumour named after him was seen in children with chronic malaria, which reduced their resistance to the Epstein Barr virus, allowing it to thrive.
But most of us live quite happily with the virus.
“If you disturb the host-virus balance in any way then changes take place which lead to very unpleasant consequences,” says Epstein.
“Once the link between Epstein Barr virus and Burkitt lymphoma was established, other seemingly unrelated conditions followed. These include a cancer at the back of the nose which is the commonest cancer seen in men in southern China and the second commonest in women in the same region.
There is also a link to Hodgkins lymphoma, a cancer of the white blood cells.
“Each one came out of the blue,” according to Epstein, “and we’ve just heard about another. About 20% of Japanese cancers of the stomach are associated with the virus.”
Yet another connection was made by Professor Dorothy Crawford, while waiting for the lift at the Royal Free hospital in London.
“It’s such a tall building everyone meets outside the lifts. I was standing next to a renal [kidney] transplant surgeon and overheard him say they’d just had their first case of post-transplant lymphoma. So I went with him to the pathology department and asked for some sections of the tissue to look at under the microscope.”
Burkitt lymphoma can now often be treated successfully with chemotherapy.
At a recent meeting in Oxford of the Epstein Barr Virus Association future directions for research were explored.
Attention is now focusing on a vaccine for the Epstein Barr virus – and some efficacy has already been demonstrated.
Epstein hopes that a vaccine will lead to the kind of success seen in other cancers caused by viruses – such as Hepatitis B and the human papillomavirus, which cause liver and cervical cancer respectively.
Johns Hopkins researchers say they have successfully used stem cells derived from human body fat to deliver biological treatments directly to the brains of mice with the most common and aggressive form of brain tumor, significantly extending their lives.
The experiments advance the possibility, the researchers say, that the technique could work in people after surgical removal of brain cancers called glioblastomas to find and destroy any remaining cancer cells in difficult-to-reach areas of the brain. Glioblastoma cells are particularly nimble; they are able to migrate across the entire brain, hide out and establish new tumors. Cure rates for the tumor are notoriously low as a result.
In the mouse experiments, the Johns Hopkins investigators used mesenchymal stem cells (MSCs)—which have an unexplained ability to seek out cancer and other damaged cells—that they harvested from human fat tissue. They modified the MSCs to secrete bone morphogenetic protein 4 (BMP4), a small protein involved in regulating embryonic development and known to have some tumor suppression function. The researchers, who had already given a group of mice glioblastoma cells several weeks earlier, injected stem cells armed with BMP4 into their brains.
In a report published in the May 1 issue of Clinical Cancer Research, the investigators say the mice treated this way had less tumor growth and spread, and their cancers were overall less aggressive and had fewer migratory cancer cells compared to mice that didn’t get the treatment. Meanwhile, the mice that received stem cells with BMP4 survived significantly longer, living an average of 76 days, as compared to 52 days in the untreated mice.
“These modified mesenchymal stem cells are like a Trojan horse, in that they successfully make it to the tumor without being detected and then release their therapeutic contents to attack the cancer cells,” says study leader Alfredo Quinones-Hinojosa, M.D., a professor of neurosurgery, oncology and neuroscience at the Johns Hopkins University School of Medicine.
Standard treatments for glioblastoma include chemotherapy, radiation and surgery, but even a combination of all three rarely leads to more than 18 months of survival after diagnosis. Finding a way to get biologic therapy to mop up what other treatments can’t get is a long-sought goal, says Quinones-Hinojosa, who cautions that years of additional studies are needed before human trials of fat-derived MSC therapies could begin.
Quinones-Hinojosa, who treats brain cancer patients at Johns Hopkins Kimmel Cancer Center, says his team was heartened by the fact that the stem cells let loose into the brain in his experiments did not transform themselves into new tumors.
The latest findings build on research published in March 2013 by Quinones-Hinojosa and his team in the journal PLOS ONE, which showed that harvesting MSCs from fat was much less invasive and less expensive than getting them from bone marrow, a more commonly studied method.
Ideally, he says, if MSCs work, a patient with a glioblastoma would have some adipose tissue (fat) removed from any number of locations in the body a short time before surgery. The MSCs in the fat would be drawn out and manipulated in the lab to secrete BMP4. Then, after surgeons removed the brain tumor, they could deposit these treatment-armed cells into the brain in the hopes that they would seek out and destroy the cancer cells.